Serum cytokine values and fatigue in chronic hepatitis C infection

Patients with chronic hepatitis C infection often experience fatigue. In many clinical situations, an association between fatigue and altered serum cytokine levels has been found. Altered cytokine levels in patients with hepatitis C have not shown a correlation with the degree of serum transaminase elevation or pathological change on liver biopsy. The aim of our study was to examine whether there was an association between abnormal serum cytokine levels and fatigue in patients with compensated chronic hepatitis C. Patients referred to a tertiary care hepatology clinic who were hepatitis C antibody positive and who had elevated alanine aminotransferase (ALT) levels were eligible for entry into the study. A control group was also included. Subjects in both groups who had characteristics other than hepatitis C that were known to alter cytokine values and/or cause fatigue were excluded. Patients completed a validated questionnaire to determine their fatigue severity score (FSS). Bioassays were used to measure interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) levels in early morning serum samples taken from patients and controls. Altered cytokine values were defined as those more than two standard deviations above the mean control value. Data was analysed using SPSS, version 8.01. Of the 78 patients with chronic hepatitis C who participated in the study, 19 (24%), 24 (30%) and 45 (56%) had elevated levels of IL-1, IL-6 and TNF-alpha, respectively, compared with only two (6%) of the control group who had elevation of any of the three cytokines. No correlation was found between the FSS and serum cytokine levels, when analysed singly or in combination, in patients with chronic hepatitis C. Hence, alteration in early morning serum levels of IL-1, IL-6 and TNF-alpha in patients with chronic hepatitis C infection and elevated ALT levels bear no correlation with the symptom of fatigue.     

Anti-Clq antibodies in patients with chronic hepatitis C infection

OBJECTIVE: Extrahepatic autoimmune features of HCV infection include autoantibody production and the development of mixed cryoglobulinemia. Anti-Clq antibody, detected with high frequency in systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, may have a direct pathogenic role in complement mediated autoimmune diseases. In this study, we investigate the prevalence of anti-Clq antibody in a population of patients with chronic HCV infection. METHODS: Serum was obtained from a group of 50 patients with chronic HCV infection and control groups comprised of patients with SLE, rheumatoid arthritis (RA), scleroderma (PSS), Sj?gren's syndrome (SS), mixed connective tissue disease (MCTD), and healthy individuals. RESULTS: Anti-Clq antibody was detected in 38% of HCV patients compared with 2% of healthy controls (p < 0.0001). Levels were also significantly elevated in patients with SLE (61%), RA (20%), PSS (15%), SS (15%) and MCTD (15%). CONCLUSION: In addition to numerous other autoantibodies, patients with chronic HCV infection exhibit increased production of anti-Clq IgG antibodies. This observation may have implications for the pathogenesis of the mixed cryoglobulinemic vasculitis syndrome.     

Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection

OBJECTIVES: To assess the potential association between hepatic iron deposition or serum iron values and hepatic fibrosis and inflammatory activity in patients with chronic hepatitis C virus infection. METHODS: In 100 consecutive patients with hepatitis C virus infection, tissue iron deposition was assessed by quantifying iron stain on liver biopsy specimens. Serum iron, ferritin, and transferrin saturation were determined by standard laboratory procedures. Statistical analyses incorporated potential confounders associated with hepatic fibrosis. RESULTS: Twenty-one patients had no fibrosis (stage 0), 13 had portal fibrosis (stage 1), 31 had periportal fibrosis (stage II), 10 had bridging fibrosis (stage III), and 25 had cirrhosis (stage IV). Positive iron stain found in liver biopsy specimens of 19 patients was associated with stage III or IV fibrosis (p = 0.004). No significant difference was found between the iron concentration or the hepatic iron index in patients with stage III or IV fibrosis compared with patients with stage I or II fibrosis. At least 1 of 3 serum iron values assessed was abnormal in 55 patients. In univariate analysis, elevated serum iron (p = 0.01), serum ferritin (p < 0.001), and transferrin saturation (p = 0.002) were associated with stage III or IV fibrosis. In multivariate analysis, the only independent predictive factor of severe hepatic fibrosis was serum ferritin (p < 0.02; odds ratio = 11.35). The serum ferritin value and tissue iron stain had a significant positive correlation (p < 0.001). CONCLUSIONS: Increased hepatic iron deposition may be associated with more advanced hepatic fibrosis in patients with chronic hepatitis C virus infection. The serum ferritin value, an independent predictor of severe hepatic fibrosis in patients with chronic hepatitis C virus infection, may predict hepatic iron deposition and severity of fibrosis.     

Re-treatment with interferon-beta of patients with chronic hepatitis C virus infection

OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.     

Renal involvement in patients with chronic hepatitis C virus infection

There is an increasing recognition of the association between chronic hepatitis C virus (HCV) infection and glomerular diseases. Renal complications may be the presenting manifestation of HCV infection. Patients may present with systemic vasculitis secondary to cryoglobulinemia, or they may present with proteinuria, microscopic hematuria, acute renal failure, or nephrotic syndrome. The pathogenesis of HCV-associated renal disease remains incompletely understood; however, deposition of HCV-containing circulating immune complexes in the glomeruli (ie, subendothelial space and mesangium) seems to play an important role. The most common renal pathology associated with HCV infection is type I membranoproliferative glomerulonephritis with or without cryoglobulinemia. In patients who do not have significant renal impairment, combination therapy with interferon-á and ribavirin is the treatment of choice. The experience with this combination therapy is quite limited in patients with renal impairment. Prolonged courses of high-dose interferon-á therapy have been successfully used for these patients; however, relapse of HCV viremia and recurrence of renal disease is common after discontinuation of therapy.     

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

Extrahepatic manifestations in patients with chronic hepatitis C virus infection

PURPOSE OF REVIEW: Chronic hepatitis C virus infection often has autoimmune clinical and analytic features. This review analyzes recent data on the close association of chronic hepatitis C virus infection with autoimmune and lymphoproliferative processes. RECENT FINDINGS: Hepatitis C virus infection has been associated with both organ-specific (thyroiditis, diabetes) and systemic autoimmune diseases. Experimental, virologic, and clinical evidence has demonstrated a close association between hepatitis C virus infection and Sj?gren syndrome, with hepatitis C virus-associated Sj?gren syndrome being indistinguishable in most cases from the primary form. With respect to rheumatoid arthritis, patients with hepatitis C virus-related polyarthritis and positive rheumatoid factor may fulfill the classification criteria for rheumatoid arthritis. Hepatitis C virus has also been associated with an atypical presentation of antiphospholipid syndrome, as well as with the development of sarcoidosis. A higher prevalence of hematologic processes in patients with hepatitis C virus infection has recently been reported, including cytopenias and lymphoproliferative disorders. Recent data are available on the use of new immunosuppressive and biologic agents (mainly mycophenolate mofetil, anti-tumor necrosis factor agents, and rituximab) in patients with hepatitis C virus infection and autoimmune or lymphoproliferative manifestations. SUMMARY: There is increasing evidence of a close association of hepatitis C virus infection with autoimmune and hematologic processes. The sialotropism of hepatitis C virus may explain the close association with Sj?gren syndrome, and its lymphotropism links the virus to cryoglobulinemia, autoimmune cytopenias, and lymphoma. The substantial overlap between cryoglobulinemic features and the classification criteria for some systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa) make the differentiation between mimicking and coexistence difficult.     

Erectile dysfunction in patients with chronic hepatitis C virus infection

Background and study aimsHepatitis C virus (HCV) infection is a major public health problem worldwide and in Egypt. Several studies have suggested that chronic HCV infection may be associated with erectile dysfunction (ED) in men. The aim of our study was to detect the prevalence of ED among male patients with chronic HCV infection.Patients and methodsThe study included 150 male patients with chronic HCV infection (124 patients with chronic hepatitis and 26 patients with HCV-associated liver cirrhosis). The Child–Pugh score was used to assess the severity of cirrhosis. An Arabic validated version of the five-item International Index of Erectile Function (IIEF-5) was used to detect the presence and severity of ED.ResultsThe patients’ age ranged from 20 to 80 years with mean age ± standard deviation (SD; 50 ± 17.19) years. The prevalence of ED among patients with chronic HCV infection was found to be 29.3%. The prevalence was significantly higher in cirrhotic as compared to chronic hepatitis patients (p < 0.001) and the average ED score was significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. There was a highly significant relation between the severity of ED and the severity of liver disease. There was a significant negative correlation between serum bilirubin and ED score and a significant positive correlation between serum albumin and ED score in patients with liver cirrhosis.ConclusionAbout 30% of patients with chronic HCV infection were found to have ED; so, given the high prevalence of HCV infection in Egypt, chronic HCV infection may be considered in the differential diagnosis of ED. There was a highly significant relation between the severity of ED and the severity of liver disease and the majority of patients with liver cirrhosis proved to be suffering from ED, which may be related to the associated hypoalbuminaemia.     

Experience with statin use in patients with chronic hepatitis C infection

We reviewed the liver enzymes of patients with chronic hepatitis C infection currently taking statin drugs. We found no significant elevation of liver enzymes during statin treatment of the 17 patients reviewed.     

Treatment of chronic hepatitis C virus infection in patients with cirrhosis

Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20–30% of patients and to hepatocellular carcinoma (HCC) in 1–5% of patients. Rates of sustained virological response with standard interferon-α (IFN-α) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients.     

Sicca complex among Egyptian patients with chronic hepatitis C virus infection

The objective of this study was to assess the prevalence of sicca complex (SC) in patients with chronic hepatitis C virus (HCV) infection and its association with clinical and laboratory features of liver disease. Subjective and objective criteria of xerophthalmia and xerostomia were investigated in 120 HCV Egyptian patients. The lacrimal gland function was assessed by: tear film break-up time and lid parallel conjunctival folds test (LIPCOF), dacroscintigraphy (DSG) for lacrimal drainage and that of salivary glands by sialoscintigraphy. Sixty six of 120 patients (55%) had SC; all (100%) were proved to have xerostomia by sialoscintigraphy and xerophthalmia detected by ophthalmologic tests. Using dacroscintigraphy all SC patients (100%) were positive for lacrimal drainage abnormalities. Only 10.1% were symptomatic for SC. None of our patients had anti-Ro or anti-La antibodies. The presence of SC was associated with older age (r = 0.28, p = 0.00), female gender (p = 0.001), cirrhosis (r = 0.34, p = 0.00), thrombocytopenia (r = −0.72, p = 0.00), and rheumatologic manifestation (p = 0.000), but not with viral load (r = 0.19, p = 0.06). DSG showed significant statistical correlation with ophthalmologic tests (r = 0.87, p = 0.00). High prevalence of SC in HCV Egyptian patients was detected. LIPCOF and DSG are objective and noninvasive methods for early diagnosis of xerophthalmia and assessment of the nasolacrimal drainage, respectively. Hindrance of lacrimal drainage proved by DSG was frequently encountered in HCV patients with SC (100%) and strongly correlated with xerophthalmia.     

慢性HBV/HCV感染人群伴随的免疫相关表现

慢性HBV/HCV感染者常常伴有自身免疫系统紊乱,在丙型肝炎中尤为常见。介绍了慢性丙型肝炎患者免疫状态紊乱的机制,出现非器官特异性自身抗体的比例,以及伴随的免疫相关疾病,如混合型冷球蛋白血症、肾小球肾炎、干燥综合征、甲状腺疾病、2型糖尿病的临床表现、诊断和治疗等。简述了慢性乙型肝炎患者免疫状态紊乱的机制、相关的免疫表现以及抗病毒治疗对其的影响。慢性乙型或丙型肝炎的抗病毒治疗可以减轻伴随的免疫系统疾病,但是不宜采用干扰素治疗,因此,乙型肝炎患者应采用核苷和核苷酸类药物治疗,丙型肝炎患者应采用直接抗病毒药物治疗。     

Immune thrombocytopenic purpura in patients with chronic hepatitis C virus infection

OBJECTIVE: Hepatitis C virus (HCV) infection has been associated with the production of autoantibodies and the development of several autoimmune disorders. Immune thrombocytopenic purpura (ITP) is an immune-mediated syndrome of unknown etiology characterized by the presence of autoantibodies against platelet membrane proteins. METHODS: Retrospective chart review. RESULTS: Seven patients with chronic HCV infection (five with cirrhosis and two with chronic active hepatitis) developed thrombocytopenia, out of proportion to their liver disease, and were diagnosed with ITP based on the presence of anti-platelet antibodies and their response to treatment. The number of patients with ITP which occurred in a population of 3440 HCV patients seen over this time interval is much greater than would be expected by chance (p < 0.00001). Six patients required treatment and four required hospitalization. Four of the six responded to corticosteroids alone. Both of the patients who failed to respond to corticosteroids responded to cyclophosphamide. No mortality occurred from complications of thrombocytopenia. CONCLUSIONS: ITP occurs more commonly in patients with chronic HCV infection than would be expected by chance. This should be considered in patients with liver disease and unexplained thrombocytopenia, as well as in patients with newly diagnosed ITP. Evaluation of antiplatelet antibodies, using an antigen-specific assay, was useful in supporting this diagnosis. Therapy with either corticosteroids or cyclophosphamide was successful in the six patients who required treatment.     

Plasma glutathione concentration in patients with chronic hepatitis C virus infection

Summary. It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-α (IFN-α) therapy in chronic hepatitis C virus (HCV) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 2 7 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.2 7 ± 0.12 μg ml^-1, HCV 1.62 ± 0.11 μg ml^-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 ± 0.007 U ml^-1, HCV 0.230 ± 0.007 U ml^-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.     

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in Western Turkey.

OBJECTIVE: The primary aim of this study was to determine the recent distribution of various genotypes of hepatitis C virus (HCV) in patients with chronic HCV infection in Western Turkey. Additional objectives were to determine whether there are any associations of genotype with gender and age, and to determine the nucleotide similarities and risk factors of non-1 HCV genotypes. METHODS: Serum samples from 345 patients (176 male, 169 female; mean age 53.3+/-12.7 years, range 10-81 years) with chronic HCV infection were analyzed in this study. Viral genotypes were determined by a restriction fragment length polymorphism (RFLP)-based in-house assay. To confirm genotypes for the samples with band patterns other than genotype 1, the 5' UTR was amplified and sequenced. RESULTS: Genotype 1 was observed in 335 of the 345 patients (97.1%). Of these, 34 patients showed infection with subtype 1a (9.9%) and 301 with subtype 1b (87.2%). Genotypes 2, 3, and 4 were determined in 0.9%, 1.4%, and 0.6% of the patients, respectively. Patients infected with type 1 were significantly older than patients infected with non-1 genotypes; however no significant differences were recorded in gender distribution. CONCLUSIONS: Genotypes other than genotype 1 are quite rare; these are possibly acquired in other countries. Turkish patients with chronic hepatitis C still represent a rather homogenous group with genotypic diversity encountered rarely.     

Treatment of chronic hepatitis C infection with cryoglobulinemia

Mixed cryoglobulinemia is characterized by a wide spectrum of manifestations that may vary from mild symptoms (such as purpura, arthralgias, and Raynaud phenomenon) to life-threatening conditions (such as acute abdomen, hyperviscosity syndrome, and renal involvement). Hepatitis C virus infection is considered the principal trigger of the disease. Therefore, the treatment not only should be tailored to the prevailing symptom but also take into account the presence of a chronic, often smoldering infection. Symptomatic therapies are to be used in cases of minor clinical manifestations and aggressive modalities in cases of life-threatening conditions. The use of aggressive cytotoxic regimens should actually be stopped and every potentially immunosuppressive drug should be used with caution. Antiviral medications are used with growing frequency. To date, a few small trials with interferon-alpha alone or in combination with ribavirin in mixed cryoglobulinemia have been conducted. This overview deals with the current approach to the management of mixed cryoglobulinemia, focusing in particular on antiviral treatment in hepatitis C virus infection with or without mixed cryoglobulinemia.